Excellent Outcome of Allogeneic Hematopoietic Stem Cell Transplantation Using a Conditioning Regimen with Medium-Dose VP-16, Cyclophosphamide and Total-Body Irradiation for Adult Patients with Acute Lymphoblastic Leukemia

Abstract

We retrospectively evaluated the outcomes of 37 adult patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (allo-SCT) conditioned with medium-dose VP-16 (VP, 30 mg/kg), cyclophosphamide (CY, 120 mg/kg), and fractionated total-body irradiation (TBI, 12 Gy) (medium-dose VP/CY/TBI). The median age of the patients was 26 years. Thirteen patients underwent transplantation from HLA-matched related donors (MRD), 18 patients underwent transplantation from HLA-matched unrelated donors (MUD), and 6 patients underwent transplantation from HLA-mismatched donors (MMD). Thirty-two patients received bone marrow and 4 patients received peripheral blood stem cells. Ten patients were Philadelphia chromosome-positive (Ph(+)) and 35 patients were in complete remission (CR) at transplantation. All of the patients achieved engraftment, and grade 3 organ toxicity before engraftment occurred in 27 patients. Grade II-III acute graft-versus-host disease (GVHD) and chronic GVHD (cGVHD) occurred in 15 and 18 patients, respectively. No patient developed grade IV acute GVHD (aGVHD) or died of GVHD. At median follow-up of 35.1 months, 32 patients were alive and all Ph(+) patients were alive. Three patients died of relapse and 2 died of transplant-related mortality (TRM). The actuarial 3-year overall survival (OS) rate, relapse rate, and TRM rate were 89.2%, 8.1%, and 5.4%, respectively. Non-CR at transplantation, MRD, and no aGVHD were significant adverse prognostic factors for survival. Medium-dose VP/CY/TBI for adult ALL patients was associated with lower relapse rate and no increase in toxicity, resulting in better survival.

Sequential chemotherapy and myeloablative allogeneic hematopoietic stem cell transplantation for refractory acute lymphoblastic leukemia

“…Bone marrow blasts were reduced as expected by DNR/VCR/PSL, so that the leukemia burden could be minimized at allo-HSCT. Administration of DNR/VCR/PSL did not apparently increase the number of severe toxicities, as compared with our previous study [1]. The high CR rates, tolerable toxicities and long-term survival rates in our study are encouraging compared with results of previous studies.…”

“…We previously reported that allogeneic hematopoietic stem cell transplantation (allo-HSCT) using a conditioning regimen with medium-dose etoposide, cyclophosphamide, and total body irradiation (VP/CY/TBI) was therapeutically promising for treating acute lymphoblastic leukemia (ALL) [1]. In that study, the 3-year overall survival rate was 88.6% when the patients underwent allo-HSCT in complete remission (CR).…”

“…Table 1. One patient had been included in our previous study [1] (Case 1). All patients received induction chemotherapy containing DNR, VCR, and PSL at least once.…”

Idarubicin-intensified BUCY2 regimens may lower relapse rate and improve survival in patients undergoing allo-SCT for high-risk hematological malignancies: a retrospective analysis

“…[6][7][8] The search for alternative regimens to the standard BUCY2 aimed at reducing the relapse rate and also TRM has proven to be difficult. [9][10][11][12] Idarubicin (IDA, 4-demethoxydaunorubicin) was first introduced as a new anthracycline and now it has been widely used to treat AML or relapsed/refractory ALL because it is more effective in multidrug-resistant cell lines and has relatively low cardiotoxicity, but a high penetration rate to central nervous system, compared with DNR or doxorubicin. 13,14 Furthermore, IDA induced a response rate as high as 43% in patients with relapsed or refractory intermediate-high-grade non-Hodgkin's lymphoma, with more than 10 months median duration of response.…”

Fludarabine, amsacrine, high-dose cytarabine and 12 Gy total body irradiation followed by allogeneic hematopoietic stem cell transplantation is effective in patients with relapsed or high-risk acute lymphoblastic leukemia

“…However, intensification of conditioning therapy before allogeneic HSCT could still be a viable approach to improve outcome, especially in young adults suffering from high-risk ALL. The composition of the intensified conditioning regimens has been rather conservative in the past, adhering basically to the standard of cyclophosphamide/TBI with the additional use of VP-16 or Ara-C. 17,[31][32][33][34] Here, we report on the first 15 patients with high-risk or refractory ALL who received allogeneic matched unrelated donor or matched sibling donor HSCT after myeloablative conditioning using a novel and more intensive conditioning regimen called FLAMSA-ATG-TBI. Our primary purpose was to evaluate practicability, safety and complication profile of this regimen as a myeloablative conditioning therapy.…”